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The U.S. Food and Drug Administration ( FDA ) has approved Kisqali ( Ribociclib ), a cyclin-dependent kinase 4/6 inhibitor, in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Approval was based on a randomized, double-blind, placebo-controlled, international clinical trial ( MONALEESA-2 ), in post-menopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who received no prior therapy for advanced disease.
A total of 668 patients were randomized to receive either Ribociclib plus Letrozole ( n=334 ) or placebo plus Letrozole ( n=334 ).
Ribociclib 600 mg or placebo was administered orally once daily for 21 consecutive days, followed by 7 days off, with Letrozole 2.5 mg administered orally once daily for 28 days.
Treatment continued until disease progression or unacceptable toxicity.

A pre-planned interim efficacy analysis demonstrated an improvement in progression-free survival ( PFS ) ( investigator-assessed ) with hazard ratio of 0.556 ( 95% CI: 0.429, 0.720; p less than 0.0001 ).
The estimated median progression-free survival had not been reached in the Ribociclib-containing arm and was 14.7 months in the placebo-containing arm.
Objective response rate ( ORR ) in patients with measurable disease was 52.7% ( 95% CI: 46.6, 58.9 ) in the Ribociclib plus Letrozole arm and 37.1% ( 95% CI: 31.1, 43.2 ) in the placebo plus Letrozole arm.
Overall survival data are immature.

The most common adverse reactions observed in 20% or more of patients taking Ribociclib were neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain.
The most common grade 3 or 4 adverse reactions ( reported in more than 2% ) were neutropenia, leukopenia, abnormal liver function tests, lymphopenia, and vomiting.
Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner.

The recommended starting dose of Ribociclib is 600 mg orally ( three 200 mg tablets ) taken once daily with or without food for 21 consecutive days followed by 7 days off treatment. ( Xagena )

Source: FDA, 2017

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